Intrinsic rifamycin resistance of<i>Mycobacterium abscessus</i>is mediated by ADP-ribosyltransferase MAB_0591

Abstract

Heterologous expression of MAB_0591 conferred rifampicin resistance to E. coli and M. tuberculosis Rifamycin MIC values were consistently lower for the M. abscessus Δarr_Mab mutant as compared with the M. abscessus ATCC 19977 parental type strain. The rifamycin WT phenotype was restored after complementation of the M. abscessus Δarr_Mab mutant with arr_Mab Further MIC data demonstrated that a C25 modification increases rifamycin activity in WT M. abscessus However, MIC studies in the M. abscessus Δarr_Mab mutant suggest that C25 modified rifamycins are still subject to modification by Arr_Mab CONCLUSIONS: Our findings identify Arr_Mab as the major innate rifamycin resistance determinant of M. abscessus. Our data also indicate that Arr_Mab-mediated rifamycin resistance in M. abscessus can only in part be overcome by C25 carbamate modification.